Role of circulating microRNA in predicting myocardial infarction

Myocardial infarction (MI) is a condition when the heart does not receive enough blood flow due to the narrowing of the blood vessels. It is also known as heart attack and caused by the plaque deposition on the arterial walls. It is a leading cause of deaths worldwide. According to several reports, micro RNA plays a critical role in myocardial infarction (Fichtlscherer et al., 2010). MicroRNA helps in controlling many biological processes and plays a role in health and heart diseases. Depletion of Dicer (a microRNA processing enzyme) leads to various defects in angiogenesis, vessel formation and cardiac development (Van Rooij and Olson, 2007). MicroRNA is detected in blood circulation and therefore can be used as potent biomarkers for cardiovascular disease (Mitchell et al., 2008). These microRNAs are also called circulating microRNA.

Circulating microRNA as biomarker

Different microRNAs are present in all developmental stages of cardiac tissues i.e. miR-21, miR-29a, miR-129, miR-210, miR-211, miR-320, miR-423, and let-7c (Thum et al., 2007). The microRNA are found circulating in body fluids like blood, saliva, urine etc. They are stable in nature and do not degrade by the endogenous RNase activity because they are protected by microRNA lipoprotein complexes forming microvesicles in the extracellular fluids (Mitchell et al., 2008).

List of micro RNAs that are either unregulated or down regulated in circulation during myocardial infarction (Khalil, Kamar and Nemer, 2017)

Figure 1: List of microRNAs that are either unregulated or down-regulated in circulation during myocardial infarction (Khalil, Kamar, and Nemer, 2017)

Some microRNA like miR-1, miR-133a, miR-133b, miR-208a, miR-499 and miR-499-5p have a prominent role as biomarkers in case of acute myocardial infarction (Romaine et al., 2015). There is a high level of this microRNA present in the blood of patients suffering from MI as compared to a healthy person. There are reports showing that circulating microRNA is present in significantly higher amounts in case of myocardial infarction (MI). This circulating miRNA provide sensitive and accurate results about the risk of myocardial infarction (MI) in an individual. But there is no incremental benefit in combining two microRNAs for the diagnosis of MI.

Pros of circulating microRNA as a biomarker for myocardial infarction (MI)

The circulating microRNA has its pros over the basic troponin assays as these assays do not give sensitive results during the intermediate phase after the onset of myocardial infarction. Also, microRNA circulating in the body fluids are not degraded easily in the environment as they are resistant to RNase digestion. They are stable in RNase-rich environment and also in extreme physical conditions like repetitive freeze-thaw cycles. It is the basic requirement for performing the cellular processes and also a prerequisite for the normal cardiac function (Dong et al., 2017).

showing advantages of circulating micro RNA over m RNA (Dong et al., 2017)

Figure 2: Advantages of circulating microRNA over mRNA (Dong et al., 2017)

Roles of circulating microRNA to predict myocardial infarction (MI)

MicroRNA is effective in rapidly detecting the myocardial infarction and helps in reducing the mortality rates. The figure below shows the characteristics that make microRNA potential biomarkers for the early diagnosis of MI.

List of characteristics is circulating micra RNA (Cheng et al., 2014)

List of characteristics is circulating micro RNA (Cheng et al., 2014)

MicroRNAs are stably present in various body fluids, like serum, plasma, saliva, tears and urine. In fact, microRNAs circulate in the serum by forming an association with RNA binding proteins or with the high-density lipoprotein (HDL) complexes. They are also present inside extracellular vesicles such as exosomes, microvesicles and apoptotic bodies that help them in circulation of the serum. These different structural associations are responsible for the extraordinary stability of microRNAs in the body fluids, which makes it an ideal biomarker. The potential of microRNAs as a novel biomarker increases by the fact that that stable microRNAs are released into extracellular compartments, especially into the bloodstream which makes its detection very easy (Ai et al., 2009).

Circulating microRNA is a potential and novel biomarker to detect the presence of myocardial infarction in an individual. The development in the research of circulating microRNA makes the diagnosis and prognosis of MI more efficient and accurate. It helps in accurately and timely treatment of the disease leading to lower mortality rates.

References

  • Ai, J. et al. (2009) ‘Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction’, Biochemical and Biophysical Research Communications, (November), p. 159. doi: 10.1016/j.bbrc.2009.11.005.
  • Cheng, C. et al. (2014) ‘MiRNAs as biomarkers of myocardial infarction: A meta-analysis’, PLoS ONE, 9(2). doi: 10.1371/journal.pone.0088566.
  • Dong, J. et al. (2017) ‘Circulating microRNAs: A novel potential biomarker for diagnosing acute aortic dissection’, Scientific Reports. Springer US, 7(1), pp. 1–11. doi: 10.1038/s41598-017-13104-w.
  • Fichtlscherer, S. et al. (2010) ‘Circulating microRNAs in patients with coronary artery disease’, Circulation Research, 107(5), pp. 677–684. doi: 10.1161/CIRCRESAHA.109.215566.
  • Khalil, A., Kamar, A. and Nemer, G. (2017) ‘MicroRNAs and Myocardial Infarct : Investigating the Controversial Role of Second Generation Biomarkers .’, 1(1).
  • Mitchell, P. S. et al. (2008) ‘Circulating microRNAs as stable blood-based markers for cancer detection’, Proceedings of the National Academy of Sciences, 105(30), pp. 10513–10518. doi: 10.1073/pnas.0804549105.
  • Romaine, S. P. R. et al. (2015) ‘MicroRNAs in cardiovascular disease: An introduction for clinicians’, Heart, 101(12), pp. 921–928. doi: 10.1136/heartjnl-2013-305402.
  • Van Rooij, E. and Olson, E. N. (2007) ‘MicroRNAs: Powerful new regulators of heart disease and provocative therapeutic targets’, Journal of Clinical Investigation, 117(9), pp. 2369–2376. doi: 10.1172/JCI33099.
  • Thum, T. et al. (2007) ‘MicroRNAs in the Human Heart’, Circulation, 116(3), pp. 258–267.
Diksha Tomer

Diksha Tomer

Research Analyst at Project Guru
She is a bachelor in Botany honours from Miranda House (Delhi University) and is pursuing her master’s in Plant Biotechnology at TERI SAS. She is a recipient of Hemendra Kothari Scholarship and her interests lie in the field of Bioinformatics and Biotechnology.
Diksha Tomer

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